Does phase 1 trial enrollment preclude quality end-of-life care? Phase 1 trial enrollment and end-of-life care characteristics in children with cancer.

BACKGROUND: End-of-life care (EOLC) discussions and treatment-related decisions, including phase 1 trial enrollment, in patients with incurable disease are complex and can influence the quality of EOLC received. The current study was conducted in pediatric oncology patients to determine whether end-of-life characteristics differed between those who were and were not enrolled in a phase 1 trial. METHODS: The authors reviewed the medical records of 380 pediatric oncology patients (aged <22 years at the time of death) who died during a 3.5-year period. Of these, 103 patients with hematologic malignancies were excluded. A total of 277 patients with a diagnosis of a brain tumor or other solid tumor malignancy were divided into 2 groups based on phase 1 trial enrollment: a phase 1 cohort (PIC; 120 patients) and a non-phase 1 cohort (NPIC; 157 patients). The EOLC characteristics of these 2 cohorts were compared using regression analysis and chi-square testing. RESULTS: A comparison of patients in the PIC and NPIC revealed no significant differences in either demographic characteristics (including sex, race, religious affiliation, referral origin, diagnosis, or age at diagnosis, with the exception of age at the time of death [P =.03]) or in EOLC indices (such as use or timing of do not attempt resuscitation orders, hospice use or length of stay, forgoing life-sustaining therapies, location of death, time from first EOLC discussion to death, and total number of EOLC discussions). CONCLUSIONS: The results of the current study of a large cohort of deceased pediatric cancer patients indicate that enrollment on a phase 1 trial does not affect EOLC characteristics, suggesting that quality EOLC can be delivered regardless of phase 1 trial participation.

Bereaved parents' intentions and suggestions about research autopsies in children with lethal brain tumors.

OBJECTIVE: To determine bereaved parents' perceptions about participating in autopsy-related research and to elucidate their suggestions about how to improve the process. STUDY DESIGN: A prospective multicenter study was conducted to collect tumor tissue by autopsy of children with diffuse intrinsic pontine glioma. In the study, parents completed a questionnaire after their child's death to describe the purpose for, hopes (ie, desired outcomes of), and regrets about their participation in autopsy-related research. Parents also suggested ways to improve autopsy-related discussions. A semantic content analytic method was used to analyze responses and identify themes within and across parent responses. RESULTS: Responses from 33 parents indicated that the main reasons for participating in this study were to advance medical knowledge or find a cure, a desire to help others, and choosing as their child would want. Parents hoped that participation would help others or help find a cure as well as provide closure. Providing education/anticipatory guidance and having a trusted professional sensitively broach the topic of autopsy were suggestions to improve autopsy discussions. All parents felt that study participation was the right decision, and none regretted it; 91% agreed that they would make the choice again. CONCLUSION: Because autopsy can help advance scientific understanding of the disease itself and because parents reported having no regret and even cited benefits, researchers should be encouraged to continue autopsy-related research. Parental perceptions about such studies should be evaluated in other types of pediatric diseases.

Impact of continuous renal replacement therapy on oxygenation in children with acute lung injury after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Acute lung injury (ALI) continues to carry a high mortality rate in children after allogeneic hematopoietic stem cell transplant (HSCT). Continuous renal replacement therapy (CRRT) is often used for these patients for various indications including renal failure and fluid overload, and may have a beneficial effect on oxygenation and survival. Therefore, we sought to determine the effect of CRRT on oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI, and to document survival to intensive care unit discharge in this at-risk population receiving both mechanical ventilation and CRRT. PROCEDURE: Retrospective analysis of a pediatric allogeneic HSCT cohort admitted to intensive care unit of a single pediatric oncology center from 1994 to 2006 who received CRRT during a course of mechanical ventilation for ALI. RESULTS: Thirty post-HSCT mechanically ventilated children with ALI who underwent CRRT were included. There was a significant improvement in PaO(2)/FiO(2) with median increase of 31 and 43 in the 24 and 48 hr intervals after initiation of CRRT compared with the 24 hr interval before CRRT (P = 0.0008 and 0.0062, respectively). This improvement in PaO(2)/FiO(2) correlated significantly with reduction of fluid balance achieved after initiation of CRRT (P = 0.0001). There was a trend not reaching statistical significance in improvement in mean airway pressure 48 hr after CRRT in survivors compared to non-survivors. CONCLUSIONS: CRRT improved oxygenation in mechanically ventilated pediatric allogeneic HSCT patients with ALI.

Outcome of severe sepsis in pediatric oncology patients.

OBJECTIVE: To describe survival to intensive care unit (ICU) discharge and 6-month survival in a large cohort of pediatric oncology patients with severe sepsis. DESIGN: Retrospective analysis. SETTING: The ICU of a single pediatric oncology center. PATIENTS: Patients with cancer admitted to the ICU of St. Jude Children's Research Hospital between January 1, 1990, and December 31, 2002, who met the following criteria: 1) severe sepsis by ACCP/SCCM (American College of Chest Physicians/Society of Critical Care Medicine) Consensus Conference criteria and 2) receipt of fluid boluses of > or =30 mL/kg to correct hypoperfusion or receipt of a dopamine infusion of >5 microg.kg.min for inotropic support. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Data evaluated were demographic variables, oncologic diagnosis and time from diagnosis to ICU admission, Pediatric Risk of Mortality III score and absolute neutrophil count at admission, use of inotropes or pressors, use of mechanical ventilation, maximum organ system failure score, blood culture results, survival to ICU discharge, and 6-month survival. We identified 446 ICU admissions of 359 eligible patients. Overall ICU mortality was 76 of 446 (17%): 40 of 132 (30%) in post-bone marrow transplant (BMT) admissions and 36 of 314 (12%) in non-BMT admissions (p < .0001). In the 106 admissions requiring both mechanical ventilation and inotropic support, ICU mortality was 68 of 106 (64%). Regarding individual patients, 6-month survival was 170 of 248 (69%) among non-BMT patients vs. 43 of 111 (39%) for BMT patients (p < .001). When the 38 patients who survived to ICU discharge after requiring both mechanical ventilation and inotropic/vasopressor support are considered, 27 (71%) were alive 6 months after ICU discharge (22 of 27 [81%] non-BMT vs. 5 of 27 BMT [19%; p < .001]). ICU mortality varied by causative pathogen, from 63% for fungal sepsis (12 of 19) to 9% (5 of 53) for Gram-negative sepsis. Logistic regression analysis of factors significantly associated with ICU mortality in admissions requiring both mechanical ventilation and inotropic support identified four variables: BMT (odds ratio, 2.9; 95% confidence interval, 1.1-7.4; p = .03); fungal sepsis (odds ratio, 10.7; 95% confidence interval, 1.2-94.4; p = .03); use of multiple inotropes (odds ratio, 4.1; 95% confidence interval, 1.4-11.8; p = .01); and Pediatric Risk of Mortality III score (odds ratio, 1.1; 95% confidence interval, 1.0-1.2; p = .04). CONCLUSIONS: In a large series of pediatric oncology patients with severe sepsis, ICU mortality was only 17% overall, although mortality remained quite high in the higher acuity patients. Mortality among the higher acuity patients was significantly associated with only a small number of variables. The number of patients alive at 6 months and the encouraging ICU survival rate further justifies the use of aggressive ICU interventions in this population.

Children's perspective on health-related quality of life during active treatment for acute lymphoblastic leukemia: an advanced content analysis approach.

BACKGROUND: Qualitative research provides insight into the cancer experience through the perspective of the pediatric patient. However, somewhat small sample sizes can hinder full discovery of new knowledge and limit interpretation of data. OBJECTIVE: The objective of this study was to describe health-related quality of life (HRQOL) reported by children and adolescents in responses to 2 interview questions during treatment for acute lymphoblastic leukemia (ALL) and compare their responses by age, gender, risk group, and time in treatment through a quantitative content analysis approach. METHODS: Children and adolescents (N = 150) were asked 2 validated questions in pediatric patients receiving treatment for ALL: "What makes a good day for you?" and "How has being sick been for you?" over 6 treatment time points. Interview data were coded analyzed quantitatively. RESULTS: Code frequencies differed significantly by age, gender, risk group, and time in treatment. Adolescents had a greater focus on being with friends, and females generally reported more codes representing negative experiences. Children and adolescents reported being affected by symptoms resulting from cancer treatment. Some adolescents described that being sick positively changed their lives and viewed their illness as a new life experience. CONCLUSION: The 2 proposed questions are feasible to use clinically to assess HRQOL in children and adolescents with ALL, and the qualitative codes from their descriptions can be used to identify factors affecting HRQOL of children and adolescents with leukemia. IMPLICATIONS FOR PRACTICE: Nurses can use these 2 questions to assess the HRQOL of children and adolescents during and following treatment for ALL.

Use of the nursing acuity score in children admitted to a pediatric oncology intensive care unit.

OBJECTIVE: To determine whether a unit specific nursing acuity score is useful for assessing patients with cancer admitted to the pediatric intensive care unit. DESIGN: Prospective, cohort analysis. SETTING: The intensive care unit of a tertiary-care pediatric oncology hospital. PATIENTS: A total of 219 patients admitted to the pediatric intensive care unit with a diagnosis of cancer or after hematopoietic stem cell transplantation. INTERVENTIONS: The nursing acuity scores obtained during the second shift after admission were recorded and compared with rates of mortality. These nursing acuity scores were also compared with the Pediatric Risk of Mortality (PRISM III) and Therapeutic Intervention Scoring System (TISS-28) scores recorded during the first day of intensive care unit admission. MAIN RESULTS: Mortality differed across the nursing acuity categories (0%, 7.5%, 20.8%, and 47.4%; p=.0002). TISS-28 and PRISM III scores progressively increased with each increase in the categorical nursing score and differed significantly among these levels (TISS-28, p=.0078; PRISM III, p=.0327). The Spearman correlation coefficients between the nursing score and TISS-28 and PRISM III were 0.432 and 0.285, respectively (p<.0001). CONCLUSIONS: The nursing acuity score accurately predicts survival in pediatric patients with cancer, correlates with established indexes of severity of illness and predictors of mortality, and identifies different mortalities across the nursing acuity categories. Although its predictive value may have been enhanced by the use of a second shift score, these findings suggest that it may be a useful tool in this patient population and affirms the insight of the bedside nurse in assessing severity of illness.

Parent-clinician communication intervention during end-of-life decision making for children with incurable cancer.

BACKGROUND: In this single-site study, we evaluated the feasibility of a parent-clinician communication intervention designed to: identify parents' rationale for the phase I, do-not-resuscitate (DNR), or terminal care decision made on behalf of their child with incurable cancer; identify their definition of being a good parent to their ill child; and provide this information to the child's clinicians in time to be of use in the family's care. METHODS: Sixty-two parents of 58 children and 126 clinicians participated. Within 72 hours after the treatment decision, parents responded to 6 open-ended interview questions and completed a 10-item questionnaire about the end-of-life communication with their child's clinicians. They completed the questionnaire again two to three weeks later and responded to three open-ended questions to assess the benefit:risk ratio of their study participation three months after the intervention. Clinicians received the interview data within hours of the parent interview and evaluated the usefulness of the information three weeks later. RESULTS: All preestablished intervention feasibility criteria were met; 77.3% of families consented; and in 100% of interventions, information was successfully provided individually to 3 to 11 clinicians per child before the child died. No harm was reported by parents as a result of participating; satisfaction and other benefits were reported. Clinicians reported moderate to strong satisfaction with the intervention. CONCLUSION: The communication intervention was feasible within hours of decision making, was acceptable and beneficial without harm to participating parents, and was acceptable and useful to clinicians in their care of families.

Factors that distinguish symptoms of most concern to parents from other symptoms of dying children.

In a previous study, we conducted telephone interviews with parents 6 to 10 months after their child's death from cancer, using open-ended questions to identify the type and frequency of cancer-related symptoms that most concerned them during the last week of their child's life. Because the parents identified many clinically striking symptoms (n=109) that were not of most concern to them, we conducted a secondary analysis of these interviews (48 mothers and four fathers of 52 patients) to identify descriptive factors associated with the parents' level of concern. Six descriptive factors were associated with symptoms of most concern and 10 factors with symptoms not of most concern. Ten of these 16 factors occurred in both categories, indicating that clinicians should directly query parents to identify the symptoms that concern parents the most. Six factors differed between the two categories, and only one (the continuous distress caused by a symptom that is unrelieved) was unique to the category of symptoms of most concern. Five factors (symptom present for at least one week, symptom not seen as remarkable by the parent or causing no distress to the child, symptom well managed, symptom improved, and symptoms for which the parent felt adequately prepared) were unique to the category of symptoms not of most concern. By inquiring about symptoms of most concern and factors that influence parental concern, clinicians may be better able to direct care efforts to reduce patients' and parents' distress and support parents during the difficult end-of-life period.

Aggressive treatment of non-metastatic osteosarcoma improves health-related quality of life in children and adolescents.

BACKGROUND: Health-related quality of life (HRQOL) of paediatric patients with osteosarcoma has not been documented longitudinally during treatment. Aims of this prospective study were to assess treatment effects on patients' HRQOL at diagnosis, during therapy and after completion of therapy, to assess sex- and age-related differences in HRQOL ratings and to assess differences between patients' and parents' reports. PATIENTS AND METHODS: Sixty-six patients (median age, 13.4 years) with newly diagnosed, localised disease completed three HRQOL instruments, and their parents completed two of the same instruments at diagnosis, before surgery (Week 12), at Week 23 and a median of 20 weeks after treatment completion. RESULTS: Significant improvements in most domains and worsening of nausea were reported by patients and parents from diagnosis to Weeks 12 and 23. Symptom distress decreased from diagnosis to Weeks 12 and 23 in 81% and 64% of patients, respectively. There were no sex- and few age-related differences in scores. Scores from patients and parents achieved good agreement. CONCLUSIONS: The HRQOL of patients improves during aggressive treatment for non-metastatic osteosarcoma, except in the domain of nausea. Clinicians can use these findings to prepare their patients for the distressing symptoms that they will likely experience at certain time points and to provide reassurance that these will significantly improve.

"Trying to be a good parent" as defined by interviews with parents who made phase I, terminal care, and resuscitation decisions for their children.

PURPOSE: When a child's cancer progresses beyond current treatment capability, the parents are likely to participate in noncurative treatment decision making. One factor that helps parents to make these decisions and remain satisfied with them afterward is deciding as they believe a good parent would decide. Because being a good parent to a child with incurable cancer has not been formally defined, we conducted a descriptive study to develop such a definition. METHODS: In face-to-face interviews, 62 parents who had made one of three decisions (enrollment on a phase I study, do not resuscitate status, or terminal care) for 58 patients responded to two open-ended questions about the definition of a good parent and about how clinicians could help them fulfill this role. For semantic content analysis of the interviews, a rater panel trained in this method independently coded all responses. Inter-rater reliability was excellent. RESULTS: Among the aspects of the definition qualitatively identified were making informed, unselfish decisions in the child's best interest, remaining at the child's side, showing the child that he is cherished, teaching the child to make good decisions, advocating for the child with the staff, and promoting the child's health. We also identified 15 clinician strategies that help parents be a part of making these decisions on behalf of a child with advanced cancer. CONCLUSION: The definition and the strategies may be used to guide clinicians in helping parents fulfill the good parent role and take comfort afterward in having acted as a good parent.

Bereaved parents' perceptions about when their child's cancer-related death would occur.

Parents of terminally ill children with cancer frequently ask clinicians when their child will die. Such information helps parents prepare for the child's death. To identify how parents perceived when their child's cancer-related death would occur, we conducted a secondary analysis of telephone interviews with 49 bereaved parents 6-10 months after their child's death to extract their descriptions of this occurrence. The parents knew in advance that their child was going to die, but they described when their child's death would occur in three different ways: anticipated (parents observed changes that alerted them that death was imminent; n=22, 52.4%), surprising (parents were surprised that their child died on that particular day; n=13, 31.0%), and overdue (parents had been waiting for the end of their child's apparent suffering; n=7, 16.7%). These categories did not differ by patients' diagnosis, sex, or location of death but differed slightly by symptom patterns. Parents who reported the occurrence of their child's death as surprising reported fewer symptom changes on the last day of their child's life, compared with the last week of life, than did the parents in the other two categories. These findings indicate that parents of children with terminal cancer can perceive when their child's death would occur very differently: Some are surprised, whereas others feel they have waited too long for their child's release from suffering. Clinicians can use these descriptions and the associated symptom patterns to help families prepare for their child's last week and last day.